Potassium Carbonate → N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220359Notes

Reaction equation

HRID 220359 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:20][CH3:21])[C:9]([C:11]([N:13]([CH:17]3[CH2:19][CH2:18]3)[CH:14]3[CH2:16][CH2:15]3)=[O:12])=[CH:10][C:5]2=[C:4]2[N:22]([CH3:25])[CH:23]=[N:24][C:3]=12.[C:26]([N:34]=[C:35]=[S:36])(=O)[C:27]1C=CC=C[CH:28]=1.C([O-])([O-])=O.[K+].[K+].BrC(C)C=O>CC(C)=O>[CH:14]1([N:13]([CH:17]2[CH2:19][CH2:18]2)[C:11]([C:9]2[N:8]([CH2:20][CH3:21])[C:6]3=[N:7][C:2]([NH:1][C:35]4[S:36][C:27]([CH3:28])=[CH:26][N:34]=4)=[C:3]4[N:24]=[CH:23][N:22]([CH3:25])[C:4]4=[C:5]3[CH:10]=2)=[O:12])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 68284Benzoyl isothiocyanateHCID 3506242-Bromopropanal3×HCID 581805034-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 58180525N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 18%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

4-Amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 1J, 86.3 mg, 0.255 mmol) was dissolved in acetone and benzoyl isothiocyanate (37.8 μL, 0.281 mmol) was added. The reaction was stirred at room temperature for 2 h. The solvent was removed in vacuo. The residue was taken up in ethanol (1500 μL) and K2CO3 (49.3 mg, 0.357 mmol) was added. The reaction mixture was warmed to 60° C. for 3 h. 2-Bromopropanal (45.4 mg, 0.332 mmol) was added. After 3 h, additional 2-bromopropanal (˜100 mg) was added. Stirred at 60° C. for 16 h. Additional 2-bromopropanal was added and the reaction mixture was stirred at 60° C. 3 h. The ethanol was removed by concentration in vacuo. The crude residue was purified by flash chromatography using an Isco 12 g column eluting with 2-10% MeOH/CH2Cl2). Additional purification was accomplished via preparative HPLC. N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methylthiazol-2-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (20 mg, 17.47% yield) was isolated as a white solid.

Workup

  1. customThe solvent was removed in vacuo
  2. temperatureThe reaction mixture was warmed to 60° C. for 3 h
  3. waitAfter 3 h
  4. stirringStirred at 60° C. for 16 h
  5. stirringthe reaction mixture was stirred at 60° C
  6. custom3 h
  7. customThe ethanol was removed by concentration in vacuo
  8. customThe crude residue was purified by flash chromatography
  9. washeluting with 2-10% MeOH/CH2Cl2)
  10. customAdditional purification

Sources & evidence

ORD record
ord-780deb0939fb4f7eb9b3cb215b207307
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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